Table of Contents......Page 0
Polymeric Biomaterials, Second Edition......Page 2
Preface......Page 5
Contributors......Page 9
Contents......Page 6
II. BACTERIAL POLYSACCHARIDES......Page 13
1. Hemodialysis......Page 15
B. Drug Delivery Systems......Page 16
V. GUAR GUM......Page 17
VI. PULLULAN......Page 18
VII. DEXTRIN AND CYCLODEXTRIN......Page 19
A. Microspheres and Microcapsules......Page 20
1. Hydroxyethyl Starch......Page 21
X. LECTINS......Page 22
IX. HYALURONIC ACID, HYALURONAN, AND HYALURONAN DERIVATIVES......Page 23
B. Alginate–Polyelectrolyte Complexation......Page 25
C. Calcium Alginate as a Matrix for Delivery of Nucleic Acids......Page 26
D. Calcium Alginate as Microparticles for Drug and Drug Proteins Delivery Systems......Page 27
F. Calcium Alginate as Tissue Engineering......Page 29
A. Xanthan Gels......Page 31
XIV. PECTIN......Page 32
XV. HEPARIN......Page 34
XVI. CHITOSAN......Page 36
A. Biocompatibility and Bioadhesivity of Chitosan......Page 37
C. Chitosan Use as a Matrix for Drug Delivery Systems......Page 38
D. Microspheres and Microcapsules......Page 39
2. Microspheres and Microcapsules for Cancer Therapy......Page 40
3. Microspheres and Microcapsules with Antiinflammatory Drugs......Page 41
E. Gels......Page 42
F. Chitosan–Polyelectrolyte Complexation......Page 43
F. Chitosan as Scaffolds......Page 48
G. Chitosan-Based Vector-DNA Complexes for Gene Delivery......Page 49
H. Chitosan Derivatives......Page 50
REFERENCES......Page 51
I. INTRODUCTION......Page 74
II. BIOFUNCTIONAL MOLECULAR BIOMIMETICS......Page 75
III. NOVEL POLYMERIC MATERIALS CONTAINING PEPTIDE/PROTEIN BIOMIMETICS......Page 77
IV. PROTEIN MATRIX AND SUBCELLULAR BIOMIMETICS......Page 83
V. BIOMIMETIC-DERIVED MATERIAL PROCESSING METHODS......Page 84
REFERENCES......Page 85
II. CHEMICAL AND PHYSICAL PROPERTIES......Page 89
III. BREAST AUGMENTATION IMPLANTS......Page 91
IV. OPHTHALMOLOGY PROCEDURES AND OPTIC DEVICES......Page 92
V. TREATMENT OF URINARY AND FECAL INCONTINENCE AND GENITOURINARY DEVICES......Page 93
VI. ORTHOPEDIC AND RECONSTRUCTIVE SURGERY......Page 94
VIII. CARDIOVASCULAR PROCEDURES AND DEVICES......Page 95
REFERENCES......Page 96
a. Synthesis......Page 101
b. Polymer Properties......Page 103
c. Biodegradation......Page 104
a. Synthesis......Page 105
c. Biodegradation......Page 106
b. Biodegradation......Page 107
1. Synthesis and Biodegradation......Page 108
C. Poly(phosphate Esters)......Page 109
1. Synthesis and Biodegradation......Page 110
1. Synthesis......Page 111
3. Crosslinked Poly(orthoesters)......Page 112
F. Polyanhydrides......Page 113
Solution polymerization.......Page 114
c. Polymer Hydrolysis......Page 115
e. Other Polyanhydrides......Page 116
1. Lactide/Glycolide Copolymers......Page 117
2. Poly(caprolactone)......Page 118
2. Pseudopoly(amino Acids)......Page 119
C. Polyphosphazenes......Page 120
E. Polyanhydrides......Page 121
REFERENCES......Page 122
I. INTRODUCTION......Page 132
II. BIODEGRADABLE BIOMATERIALS HAVING NITRIC OXIDE FUNCTION......Page 133
A. Synthesis and Characterization......Page 134
B. In Vitro Hydrolytic Degradation......Page 135
C. In Vitro Biological Activity on Human Smooth Muscle Cells......Page 138
REFERENCES......Page 139
A. Classi.cation......Page 141
1. Water Content and Swelling Ratio......Page 142
B. Contact Lens......Page 143
A. Drug Delivery System......Page 144
A. Immunoisolation......Page 145
B. Tissue Engineering......Page 146
1. Overview......Page 147
D. Novel Hydrogels......Page 148
REFERENCES......Page 149
II. MUCUS GEL COMPOSITION......Page 154
1. Interpenetration......Page 156
a. Rotating Cylinder......Page 157
3. Rheological Techniques......Page 158
1. Anionic Polymers......Page 159
2. Cationic Polymers......Page 160
4. Ambiphilic Polymers......Page 161
B. Covalent Binding Polymers......Page 162
A. Mucoadhesion and Enzyme Inhibition......Page 164
C. Mucoadhesion and Buffer System......Page 166
D. Mucoadhesion and Controlled Release......Page 167
REFERENCES......Page 169
A. Tissue Engineering and the Concept of the Scaffold......Page 173
B. Biological Properties......Page 174
C. Collagen Scaffolds......Page 175
A. General Overview......Page 176
1. Chemical and Physical Properties......Page 177
3. Immunology and the Tissue Response......Page 178
2. Interactions with Biomolecules and Cells......Page 179
4. Formation of Tissue Scaffolds......Page 180
1. General......Page 182
2. Interactions with Enzymes......Page 183
5. The Tissue Response to GAG-Containing Biomaterials......Page 184
IV. POLY( -HYDROXY ACIDS)......Page 185
VI. POLYETHYLENE GLYCOL......Page 186
REFERENCES......Page 187
B. Origin......Page 193
A. Solutions......Page 194
2. Role of Molecular Weight......Page 195
3. Role of Other Parameters......Page 196
1. Physical Gels......Page 197
b. Chitin Gels......Page 198
1. Crystallinity of Chitosan......Page 199
b. Films......Page 201
III. PHYSICOCHEMICAL PROPERTIES......Page 202
1. General Aspects......Page 203
3. Polyelectrolyte Complexes......Page 204
2. Hemocompatibility......Page 205
4. Bacterio- and Fungistatic Properties......Page 206
2. Immunological Properties in Animals......Page 207
A. Cosmetics......Page 208
2. Effect on Intestinal Media......Page 209
5. Fat Binding and Antilipidic Metabolism......Page 210
C. E-3-Pharmacology......Page 211
2. Chitosan as an Enhancer of the Permeability of Epithelial Tissues......Page 212
1. Cell Activation......Page 213
3. Osteogenesis by Chitosan......Page 214
REFERENCES......Page 215
D. Physicochemical and Biological Properties of Chitosan......Page 219
2. Bioadhesive Bilayered Devices as Baccal Drug Delivery Systems......Page 221
3. Poly(Vinyl Alcohol) Gel Spheres Containing Chitosan......Page 222
5. Bioadhesion of Hydrated Chitosans......Page 223
8. Chitosan-EDTA Linked with Bowman-Birk Inhibitor......Page 224
10. Chitosan Glutamate as an Absorption Enhancer of 9-Desglycinamide, 8-L-Arginine Vascopressin......Page 225
A. Definition of Hydrogels......Page 226
3. Chitosan-Poly(Ethylene Glycol Diacrylate Semi-IPN......Page 227
B. Nonviral Delivery Systems......Page 228
3. Complex Coacervation of DNA with Chitosan......Page 229
7. Lactosylated Chitosan for Cell Targeting......Page 230
1. Chitosan Nanoparticles as a Novel Carrier for Vaccines......Page 231
B. Chitosan as a Mucosal Adjuvant......Page 232
2. Interfacial Acylation......Page 233
6. Solvent Evaporation......Page 234
2. Local Implantation of Chitosan Microspheres Containing Bisphosphonates......Page 235
5. N-Succinyl-Chitosan-Mitomycin C as an Implant......Page 236
1. Improvement of Insulin Absorption Using Chitosan......Page 237
VII. CONCLUSION......Page 238
REFERENCES......Page 239
I. INTRODUCTION......Page 244
2. Synthetic Supports......Page 246
B. Functionalization......Page 247
III. DEPOSITION OF ANTIFOULING LAYERS......Page 250
B. Silver as an Antimicrobial Molecular Recognition Agent......Page 258
IV. SURFACE FUNCTIONALIZATION OF BIOMATERIALS USING A COLD PLASMA APPROACH......Page 259
B. Plasma Chemistry......Page 260
V. PLASMA TECHNOLOGIES FOR THE PREVENTION OF PROTEIN ADSORPTION, BACTERIAL ATTACHMENT, AND BIOFILM FORMATION......Page 261
A. Plasma-Enhanced Modification of Polymeric Substrates......Page 264
B. Silver Deposition on Polymers......Page 266
C. DMP Plasma Generation of Colloidal Silver......Page 267
VI. PLASMA-MEDIATED IMMOBILIZATION OF ACTIVE BIOMOLECULES......Page 269
A. Plasma Functionalization of Natural and Synthetic Supports......Page 272
B. Plasma-Assisted Development of Biosensors......Page 279
C. Synthesis of Oligonucleotides from Plasma-Funtionalized Surfaces......Page 290
REFERENCES......Page 292
A. The Dendritic Molecular Architecture......Page 296
B. Theoretical Models and Experimental Characterization of Dendrimers......Page 298
C. Synthetic Strategies in Dendrimer Chemistry......Page 299
1. The B Factor, Practical Alternative to the Cooperativity a Factor......Page 300
2. Enthalpy and Entropy in Multivalent Interaction......Page 303
B. Dendrimer–Carbohydrate Conjugates......Page 304
C. Dendrimer–Peptide Conjugates......Page 307
D. Dendrimer-Oligonucleotide and -Nucleic Acid Conjugates......Page 309
REFERENCES......Page 312
a. The Various Families of Elastomers......Page 316
b. Very Special Elastomers......Page 317
b. Polymerization......Page 318
Copolymerization.......Page 319
e. Elastomer Reinforcement......Page 320
2. Manufacture......Page 321
4. Copolymerization of Silicone Elastomers......Page 322
5. Fillers......Page 323
c. Denucleation of Silicone Elastomers......Page 324
2. Manufacture......Page 325
3. Mechanical Behavior of Polymethane Elastomers......Page 326
4. Biodegradation of Polyurethane Elastomers......Page 327
5. Biostable Polyurethane Elastomers......Page 328
7. Modi.ed Polyurethane Elastomers......Page 330
D. Saturated Polyesters and Copolyesters......Page 331
F. Polyole.ns......Page 332
I. Hydrogels......Page 333
L. Polyamides......Page 334
N. Fluorinated Elastomers......Page 335
A. Introduction......Page 337
b. Sterilization......Page 339
d. Tests......Page 340
b. Animals......Page 341
f. Implantation......Page 342
b. Tests......Page 343
5. Reproduction and Embryo Development Assays......Page 344
A. Elastomers in General......Page 345
1. Protein Adsorption......Page 346
2. Adherence and Activation of Inflammatory Cells......Page 348
3. Local Complications......Page 349
1. Degradation......Page 350
2. Carcinogenic Reactions......Page 351
D. Silicones......Page 352
E. Polyurethanes......Page 353
I. Polytetra.uoroethylene......Page 356
REFERENCES......Page 357
A. Cell Adhesion......Page 366
4. Integrins......Page 367
b. Ligation......Page 368
c. Focal Adhesions......Page 369
d. Growth Factors......Page 370
III. MODIFICATION OF BIOMATERIAL SURFACES: CHEMICAL CONSIDERATIONS......Page 371
A. Physicochemical Modi.cations......Page 372
C. Morphological Modi.cations......Page 373
2. Surface Roughness......Page 374
1. Composition......Page 375
V. CONCLUSIONS......Page 376
REFERENCES......Page 377
I. INTRODUCTION......Page 381
2. Keratoconjunctivitis Sicca......Page 382
4. Endophthalmitis......Page 383
A. Polymeric Gels......Page 384
a. Cellulose Derivatives......Page 385
b. Polyacrylic Acid......Page 386
c. Sodium Hyaluronate......Page 388
d. Poly(Vinyl Alcohol)......Page 389
2. In Situ Forming Gels......Page 390
a. Gelling Activated by pH Change......Page 391
b. Gelling Activated by Temperature Change......Page 392
c. Gelling Activated by Electrolyte Composition Change......Page 394
4. Ocular Tolerance of Hydrogels......Page 395
B. Dispersed Systems......Page 396
C. Inserts......Page 397
1. Soluble Inserts......Page 398
b. Synthetic and Semisynthetic Polymers......Page 400
a. Reservoir Inserts......Page 401
b. Matrix Inserts......Page 402
3. Bioerodible Inserts......Page 403
a. Poly(Lactic Acid), Poly(Glycolic Acid) and Their Copolymers......Page 404
b. Polycaprolactones......Page 406
c. Polyanhydrides......Page 407
a. Ethylene Vinyl Acetate......Page 408
1. Third Generation Poly(Ortho Esters)......Page 409
a. Nanoparticles......Page 410
b. Microspheres......Page 411
REFERENCES......Page 413
I. INTRODUCTION......Page 426
II. ORAL BIOLOGY AND BIOCHEMISTRY......Page 427
III. TESTING AND EVALUATION OF MATERIALS FOR DENTISTRY......Page 433
1. Bases, Liners, and Varnishes for Cavities......Page 435
a. Composite Resins......Page 437
3. Bonding to Dental Structures......Page 438
B. Endodontic Treatment......Page 439
A. Removable Dental Prosthetic Bases......Page 440
A. Bone Loss Replacement, Fracture Immobilization, and Facial Outward Prostheses......Page 441
C. Sutures......Page 442
VII. PERIODONTOLOGY......Page 443
A. Guided Tissue Regeneration......Page 444
VIII. ORTHODONTICS AND OTHER APPLICATIONS......Page 445
IX. NEW PERSPECTIVES......Page 446
REFERENCES......Page 447
II. STRUCTURE AND FUNCTION OF THE SKIN......Page 454
C. Xenograft......Page 455
IV. PERMANENT SKIN SUBSTITUTES......Page 456
A. Dermal Substitutes......Page 457
C. Composite Substitutes......Page 458
REFERENCES......Page 459
I. INTRODUCTION......Page 462
2. Basement Membrane Zone......Page 463
a. Regulation of Epidermopoiesis: Stimulatory Factors......Page 464
1. Sensory System......Page 465
2. Vascular System......Page 466
a. Melanin: Types, Synthesis, and Hormonal Regulation......Page 467
b. Photobiology and Photochemistry of Melanogenesis......Page 468
d. Melanin, Melanogenesis, and Skin Photoprotection......Page 469
a. The Role of Lipids in the Structure and Junctional Organization of the Horny Layer......Page 470
C. Ultrastructure of the Dermoepidermal Junction......Page 472
3. Biochemical-Molecular Aspects of Biosynthesis of Collagen and Elastin......Page 473
5. Ground Substance Biosynthesis and the Role of Structural Proteins, Glucosarninoglycans, and Proteoglycans......Page 475
4. Sebaceous Glands......Page 477
B. Skin and Hydration......Page 478
C. Skin and Defense System......Page 480
1. Implications for the Cosmetic Industry......Page 481
a. Functional Properties......Page 483
b. Structure......Page 484
Gum tragacanth.......Page 485
Gum ghatti.......Page 486
Carrageenans.......Page 487
Xanthan gum.......Page 488
Hydroxyethyl cellulose.......Page 489
f. Melanin......Page 490
REFERENCES......Page 491
I. INTRODUCTION......Page 494
A. Chemical Structure and Manufacturing Processes......Page 495
1. Catgut and Reconstituted Collagen Sutures......Page 497
2. Polyglycolic Acid Suture (Dexon) and Poly(glycolide-lactide) Copolymer Suture (Vicryl)......Page 499
3. Poly-p-dioxanone Suture (PDS & PDS II)......Page 502
6. Poly (glycolide-L-lactide) Copolymer Suture (Panacryl)......Page 503
8. Silk Suture......Page 504
9. Polyester-Based Sutures......Page 505
10. Polyamide Based Sutures......Page 506
11. Polypropylene Sutures......Page 507
13. Poly (Hexafluoropropylene- VDF) Suture (Pronova)......Page 508
14. Stainless Steel Sutures......Page 509
B. Size Classi.cation of Sutures......Page 510
C. Physical Configuration and Surface Treatments......Page 511
D. Physical and Mechanical Properties......Page 512
E. Handling Properties......Page 515
F. Biological Properties......Page 516
G. Biodegradation and Absorption Properties......Page 519
III. SURGICAL MESHES......Page 522
A. Nonabsorbable Surgical Meshes......Page 523
B. Absorbable Surgical Meshes......Page 528
A. Introduction......Page 530
1. Totally Absorbable Based Vascular Grafts......Page 531
2. Partially Absorbable Based Vascular Grafts......Page 533
3. Mathematical Modeling of Porosity of Vascular Fabrics......Page 537
REFERENCES......Page 540
II. BIOABSORBABLE SYNTHETIC POLYMERS AND THEIR PROPERTIES......Page 548
A. Suture Materials......Page 549
IV. DEVELOPMENT OF SELF-REINFORCED BIOABSORBABLE COMPOSITES AND THEIR PROPERTIES......Page 550
V. BIOABSORBABLE FIXATION IN FRACTURE TREATMENT......Page 553
VI. BIOABSORBABLE FIXATION IN ORTHOPEDIC SURGERY......Page 555
VII. BIOABSORBABLE FIXATION IN TRAUMATOLOGY AND ORTHOPEDIC SURGERY IN CHILDREN......Page 557
VIII. BIOABSORBABLE FIXATION IN SUPPORTING SOFT TISSUE INJURIES......Page 558
IX. COMPLICATIONS OF BIOABSORBABLE IMPLANTS......Page 559
REFERENCES......Page 560
A. History of Arti.cial Joints......Page 566
B. Ultra-High Molecular Weight Polyethylene for Articulating Surfaces......Page 567
1. Structure and Properties of UHMWPE......Page 568
3. Processing of UHMWPE......Page 569
c. Direct Compression Molding......Page 571
f. Oxidation......Page 573
4. Wear Properties of UHMWPE......Page 575
5. Fatigue Properties of UHMWPE......Page 577
a. Cross-Linking......Page 579
II. BONE CEMENT......Page 580
B. Chemical Composition......Page 581
1. Introduction......Page 582
4. Discussion......Page 583
F. Intramedullary Plug......Page 586
REFERENCES......Page 588
I. ARTIFICIAL HEART VALVE PROSTHESES......Page 592
1. Choice of Valve Type......Page 594
C. Choice of Material......Page 595
A. In Vitro Steady Flow Studies......Page 597
C. In Vitro Pulsatile Flow Evaluation......Page 598
D. Closing Volume Measurement......Page 599
E. Closing Impact Force Measurements......Page 600
A. Mechanical Valve Closing Dynamics and Induced Stresses......Page 601
V. ACCLERATED DURABILITY TESTING FOR WEAR AND FATIGUE RESISTANCE......Page 605
A. Animal Studies......Page 607
1. Patients......Page 608
6. Postoperative NYHA Status (Figure 12)......Page 609
7. Valve-Related Mortality and Late Events......Page 610
REFERENCES......Page 611
I. INTRODUCTION......Page 614
A. Extrinsic Pathway and Primary Hemostasis......Page 616
B. Intrinsic Pathway and the Contact System......Page 617
E. The Fibrinolytic System......Page 618
1. Circulating Coagulation Inhibitors......Page 619
G. Procoagulant Regulation......Page 620
A. Role of the Adsorption of Protein......Page 621
IV. THE INFLAMMATORY RESPONSE......Page 623
1. The Complement System......Page 624
2. Biodegradation......Page 625
B. Soluble Polymers......Page 626
B. Polymers with Antitumor Activity......Page 627
A. Chemical Modi.cation of Polymers......Page 628
2. Graft Polymerization......Page 629
IX. HEMOCOMPATIBILITY OF POLYMERS......Page 630
B. Blood Compatibility and Protein Adsorption......Page 631
D. Anticoagulant Drug-Releasing Materials......Page 632
E. Covalent Binding of Anticoagulant Drugs to Polymers......Page 633
F. Heparinlike Materials......Page 634
G. Polymers and the Immune Response......Page 635
X. CONCLUSION......Page 636
REFERENCES......Page 637
II. POLYESTER (DACRON): CHARACTERISTICS AND APPLICATIONS......Page 650
IV. CLINICAL AND RESEARCH OBSERVATIONS: BASIS FOR RESEARCH......Page 651
A. Prevention of Surface Thrombus Formation......Page 652
VI. MODIFICATION OF DACRON: CREATION OF \"ANCHOR\" SITES......Page 653
VII. SELECTION OF PROTEIN FOR \"BASECOAT\" LAYER ON DACRON SURFACE......Page 654
B. Recombinant Vascular Endothelial Growth Factor (VEGF)......Page 655
A. Covalent Linkage of 128I-BSA with Various Sulfo-SMCC Rations to HD Surfaces Via EDC Cross-linker......Page 656
C. Initial Determination of Antithrombin Activity by Modified Dacron Surfaces......Page 657
D. Characterization of Antithrombin Activity of the 1:50 HD-BSA-SMCC-S-rHir Segments......Page 658
E. In Vitro Flow Study......Page 659
F. In Vivo Assesment of a Dacron-BSA-SMCC-S-128I-rHir Surface in a Thoracic Aorta Patch Model......Page 660
A. Creation of Soluble VEGF Conjugate for Biological Activity Studies......Page 661
B. Comparison of Mitogenic Activity Between VEGF, VEGF-SH, and CSA-VEGF......Page 662
C. Comparison of Migration Properties of Native Versus Complex Bound VEGF......Page 663
D. Covalent Linkage of 128I-Collagen/128I-Collagen-SMCC to HD Segments......Page 664
F. Assesment of In Vivo Mitogenic Properties of Surface-Bound VEGF......Page 665
XI. CONCLUSIONS FROM RESEARCH......Page 666
REFERENCES......Page 667
I. INTRODUCTION......Page 671
A. Antithrombin Chemical Structure......Page 674
B. Antithrombin Functional Biochemistry......Page 675
A. Heparin Chemical Structure......Page 677
B. Heparin Functional Biochemistry......Page 678
A. Limitations of Currently Available Anticoagulants......Page 680
B. Potential Advantages of Covalent Antithrombin-Heparin Complexes......Page 681
C. Potential Uses of Covalent Antithrombin-Heparin Complexes......Page 682
D. Concepts for Producing Covalent Antithrombin-Heparin Complexes......Page 683
A. Chemistry, Physicochemical Properties, and In Vitro Activity......Page 684
B. In Vivo Performance......Page 690
A. Biochemical and Chemical Overview......Page 692
B. Characteristics of Coated Surfaces......Page 693
VII. THE FUTURE......Page 695
REFERENCES......Page 696
A. Introduction......Page 705
a. Surface Properties......Page 707
2. Wound Management Indications......Page 708
3. Transdermal Drug Delivery......Page 710
4. Trauma-Free Removal......Page 712
1. Acrylic Polymers......Page 714
2. Rubber-Based PSAs......Page 716
a. Sutures and Staples......Page 717
3. Factors Influencing the Choice of Tissue Adhesives......Page 718
b. The Role of Cynoacrylates in the Medical Market......Page 719
c. Mechanism of Bonding......Page 720
e. Issues of Toxicity in Cyanoacrylates......Page 721
a. Polyurethane Adhesives......Page 723
b. Gelatin-Resorcinol-Formaldehyde (GRF) Adhesives......Page 724
a. Bioabsorbable Synthetic Hydrogels as Surgical Sealants......Page 725
1. Fibrin Tissue Adhesives......Page 726
Fibrinolytic Inhibitors.......Page 727
d. Mechanical and Adhesive Properties......Page 728
e. Fibrin Adhesives as Delivery Vehicles......Page 729
a. Mussel Adhesive Proteins......Page 730
b. Synthetic Analogues of Protein Adhesives......Page 731
IV. CONCLUSIONS......Page 733
REFERENCES......Page 734
B. Environment-Sensitive Hydrogels......Page 740
II. GLUCOSE-SENSITIVE HYDROGELS FOR SELF-REGULATED INSULIN DELIVERY......Page 741
2. Complexes of Con A and Glucose-Containing Polymers......Page 742
3. Sol–Gel Phase-Reversible Hydrogels......Page 743
B. Phenylboronic Acid as a Glucose-Responsive Unit......Page 744
1. Hydrogels Made of Cationic Polyelectrolytes......Page 745
3. Hyrdogels Made of pH/Temperature-Sensitive Polymers......Page 746
III. GLUCOSE-SENSITIVE HYDROGELS AS GLUCOSE SENSORS......Page 747
REFERENCES......Page 749
I. INTRODUCTION......Page 754
A. Delivery of Cholecystokinin (CCK) Analogs......Page 756
B. Delivery of Vaccines......Page 757
a. Nanosphere Preparation by Polymerization of Monomers......Page 758
b. Preparation of Nanospheres from Preformed Polymers......Page 759
2. Therapeutic Applications of Nanospheres......Page 760
b. Application to the Treatment of Cancer......Page 761
c. Nanospheres for Oligonucleotide Delivery......Page 763
b. Characterization of Nanocapsules......Page 764
Improvement of biological response.......Page 766
c. Ocular Delivery......Page 767
a. In Vitro Experiments......Page 768
b. In Vivo Considerations......Page 769
2. Specific Bioadhesive Interactions of Nanoparticles......Page 770
D. Nanoparticles Avoiding Uptake by Phagocytic Cells......Page 771
REFERENCES......Page 773
A. Properties of Amphiphiles, Bilayers, and Liposomes......Page 783
1. Zwitterionic and Anionic Lipids......Page 786
1. Thermodynamic Properties of Pure Lipids......Page 787
II. TECHNIQUES OF LIPOSOME PREPARATION......Page 790
A. Mechanical Dispersion by Direct Hydration (MLVs)......Page 791
C. Sonication (SUVs)......Page 792
E. Reverse-Phase Method......Page 793
G. Mechanism of Lipid Vesicle Formation......Page 794
III. METHODS FOR DRUG LOADING......Page 795
C. Reconstitution of Proteins......Page 796
1. Active Loading by pH Gradient......Page 797
4. Theoretical Explanation of Remote Loading......Page 798
IV. CHARACTERIZATION OF LIPOSOMES......Page 800
A. Visual Examination......Page 801
B. Size Determination of Liposomes......Page 802
D. Measurement of Trapped Volume, Trapping Efficiency, and Solute Release......Page 803
V. TYPES OF LIPOSOMES ACCORDING TO FUNCTIONALITY......Page 804
B. Sterically Stabilized Liposomes......Page 805
D. Activosomes or Polymorphic Liposomes......Page 807
VI. LIPOSOMES AS DRUG DELIVERY VEHICLES......Page 808
A. Liposomes in Infectious Diseases......Page 809
B. Liposomes in Anticancer Therapy......Page 811
1. The Formation of Genosomes (Lipoplex)......Page 813
3. Formation of Lipid-DNA Particles via Hydrophobic Intermediates......Page 814
4. Stabilized Plasmid–Lipid Particles......Page 816
4. Other Applications: Vaccination and Diagnostics......Page 817
REFERENCES......Page 818
I. INTRODUCTION......Page 822
A. Drug Permeability Barrier and Solubilization Properties of the Bilayer Membrane......Page 823
B. Effects of Steric Stabilizing Lipids on PK and Therapeutic Properties of Liposomal Anticancer Agents......Page 827
C. Multifunctional Liposomes; Targeted, Fusogenic, and Controlled Release Systems......Page 830
B. Development of Liposomal Vincristine......Page 832
1. Liposomal Anticancer Drugs Alone......Page 833
3. Liposomal Anticancer Drugs Combined with Conventional PGP Inhibitors......Page 834
IV. FUTURE DIRECTIONS......Page 835
REFERENCES......Page 836
II. PLASMA CIRCULATION AND EXTRAVASATION OF POLYMERS AND OTHER MACROMOLECULES......Page 841
IV. TUMOR VASCULAR PERMEABILITY AND THE EPR EFFECT......Page 842
VI. SIGNIFICANCE OF THE DRUG-POLYMER LINKAGE......Page 843
A. Systemic Distribution of Cationic Lipid/DNA Complexes......Page 844
XIII. CONCLUSIONS......Page 845
REFERENCES......Page 846
I. INTRODUCTION: DRUG TARGETING IN ANTICANCER CHEMOTHERAPY USING MACROMOLECULAR CARRIERS......Page 849
B. Bioconjugation Methods Used for the Preparation of Drug-Carrier Conjugates......Page 851
a. Polypeptides (Proteins)......Page 852
c. Antibodies......Page 854
c. Introduction of Carboxylic Groups......Page 855
C. Group-Speci.c Coupling Reactions......Page 856
a. Maleimides......Page 857
c. Pyridyl Disul.des......Page 858
3. Carboxylic Acid Groups......Page 859
D. Incorporation of a Predetermined Breaking Point Between Drug and Carrier......Page 860
A. Introduction......Page 861
2. Antibodies as Targeting Moieties......Page 862
C. Clinical Trials with Chemoimmunoconjugates......Page 863
1. Doxorubicin-BR96-Immunoconjugate......Page 865
3. Immunoconjugates with Desacetylvinblastine......Page 866
7. Neocarzinostatin-Immunoconjugate......Page 867
D. Strategies for Enhanced Antibody Delivery to Tumors......Page 868
2. Regional Administration of Immunoconjugates......Page 869
IV. DRUG CONJUGATES WITH SERUM PROTEINS......Page 870
A. Drug Conjugates with Growth Factors......Page 872
a. Epidermal Growth Factor (EGF)......Page 873
b. Transforming Growth Factor α (TGF-α)......Page 874
3. Fibroblast Growth Factor (FGF)......Page 875
2. Immunotoxins with Interleukin-4......Page 876
A. Dextrans......Page 878
1. Dextran Conjugates with Anthracyclines and Mitomycin C......Page 879
VII. SUMMARY......Page 880
REFERENCES......Page 881
I. INTRODUCTION......Page 892
A. Antibody-Directed Enzyme-Prodrug Therapy (ADEPT)......Page 896
B. Gene-Directed Enzyme-Prodrug Therapy (GDEPT)......Page 899
C. Targeting by Means of Polymers......Page 904
D. Antimetabolite with Inactivation of Rescue Agent at Cancer Sites (AMIRACS)......Page 909
III. CONCLUSIONS......Page 911
REFERENCES......Page 914
I. INTRODUCTION......Page 925
II. CATIONIC LIPOSOMAL VECTORS......Page 926
1. Effect of Polymers......Page 928
2. Effect of Lipid......Page 929
4. In Vivo gene transfer with LPD-I......Page 930
B. Anionic Liposome-Entrapped, Polycation-Condensed DNA (LPD-II)......Page 931
C. Advantages and Limitations......Page 932
C. Targeted Delivery of Naked DNA......Page 933
V. SUMMARY AND CONCLUSION......Page 934
REFERENCES......Page 935
II. GENE DELIVERY BY LIPOPLEXES IN CELL CULTURE......Page 938
IV. GENE DELIVERY BY LIPOPLEXES IN VIVO......Page 942
VI. MECHNISMS OF AND BARRIERS TO LIPOPLEX-MEDIATED GENE DELIVERY......Page 944
VII. STRATEGIES FOR THE ENHANCEMENT OF LIPOPLEX-MEDIATED GENE DELIVERY......Page 945
B. Use of Nuclear Localization Signal (NLS) Peptides......Page 946
C. Facilitation of Gene Transfer by Membrane-Destabilizing or Fusogenic Peptides......Page 947
CONCLUDING REMARKS......Page 948
REFERENCES......Page 949
I. INTRODUCTION......Page 954
A. pH-Responsive Hydrogels......Page 955
B. Temperature-Responsive Hydrogels......Page 956
A. Glucose Oxidase–Containing Hydrogels......Page 957
B. Hydrogels with Phenylboronic Acid Moiety......Page 959
C. Lectin-Containing Hydrogels......Page 961
IV. ANTIGEN-RESPONSIVE HYDROGELS......Page 963
A. Molecular Imprint Hydrogels......Page 965
B. Other Biomolecule-Responsive Hydrogels......Page 966
REFERENCES......Page 967
B. Polyethylenimine......Page 970
c. Galactose-Modi.ed Materials.......Page 971
A. Delivery of Medications......Page 972
A. Coupling of Fusogenic Proteins......Page 973
REFERENCES......Page 974
A. Field of Application of the BAP......Page 977
II. DM: EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL FEATURES......Page 978
B. Islet Cell Transplantation......Page 979
V. THE BAP: GENERAL FEATURES......Page 981
A. Macrodevices......Page 982
1. Technical Procedures......Page 983
3. Pitfalls......Page 984
Role of cellular immunity.......Page 985
Autoimmune recurrence of disease.......Page 986
2. Not Immunomediated......Page 987
B. Biocompatibility and Specific Aspects of Membrane Configuration......Page 988
2. Chemistries......Page 989
c. Agarose......Page 990
e. Other Polymers......Page 991
h. MSM......Page 992
3. Microcapsules: Summary of Current Issues and Outlook......Page 993
IX. CONCLUSION......Page 996
REFERENCES......Page 997
I. SKIN ANATOMY......Page 1000
II. PERCUTANEOUS ABSORPTION PATHWAYS......Page 1001
B. Transcellular vs. Intercellular Pathways......Page 1002
IV. TRANSDERMAL THERAPEUTIC SYSTEMS......Page 1003
A. Drug Candidate Selection......Page 1004
1. Membrane-Moderated Transdermal Drug Delivery Systems (MMT)......Page 1005
3. Adhesive Dispersion-Type Transdermal Drug Delivery Systems (ADT)......Page 1006
4. Microreservoir Dissolution-Controlled Transdermal Drug Delivery System (MDCT)......Page 1007
1. Water......Page 1008
3. Amides......Page 1009
5. Urea and Analogs......Page 1010
7. Azone and Its Analogues......Page 1011
9. Surfactants......Page 1012
12. Terpenes......Page 1013
14. Polymeric Enhancers......Page 1014
1. Phonophoresis......Page 1015
3. Electroporation......Page 1016
REFERENCES......Page 1017
II. CHARACTERISTICS OF MUCOUS MEMBRANE (1,2)......Page 1024
A. Surface Epithelium......Page 1025
A. Mechanisms......Page 1026
2. Metabolic Barrier......Page 1027
b. Action on Tight Junction (Enhanced Paracellular Transport)......Page 1028
c. Action on the Membrane Structure (Enhanced Transcellular Transport)......Page 1029
3. Examples......Page 1030
2. Major Biological Barriers and Appropriate Strategies......Page 1032
3. Examples......Page 1033
3. Examples......Page 1035
1. Relevant Anatomy and Physiology......Page 1037
2. Major Biological Barriers and Appropriate Strategies......Page 1039
3. Examples......Page 1040
1. Relevant Anatomy and Physiology......Page 1044
3. Examples......Page 1045
REFERENCES......Page 1046
II. NONSPECIFIC AND SPECIFIC BIOADHESION......Page 1056
III. MECHANISMS OF BIOADHESION......Page 1057
IV. DETERMINATION OF BIOADHESIVE FORCE OF ATTACHMENT......Page 1058
VI. BIOADHESIVE (MUCOADHESIVE) POLYMERS FOR PHARMACEUTICAL APPLICATIONS......Page 1060
B. Cross-linking......Page 1061
E. Segment Mobility/Flexibility......Page 1063
H. Polymer Combinations......Page 1064
A. Bioadhesive Devices for the Oral Cavity......Page 1065
B. Bioadhesive Devices for the Gastrointestinal Tract......Page 1067
C. Bioadhesive Devices for Rectal Drug Delivery......Page 1068
E. Bioadhesive Devices for Vaginal Drug Delivery......Page 1069
G. Bioadhesive Devices for Ocular Drug Delivery......Page 1070
REFERENCES......Page 1071
A. Problems with Hydrophilic Agents......Page 1075
2. Implants......Page 1076
4. Micro- and Nanoparticles......Page 1077
1. Genetically Engineered Cells......Page 1078
A. Biodegradable Block Copolymers for Development of Micellar Delivery Systems......Page 1079
B. Micelles for the Delivery of Neuroactive Agents......Page 1080
1. Problems in the Delivery of Antisense Oligonucleotides......Page 1081
3. Delivery of Antisense Oligonucleotides Employing Copolymers......Page 1083
REFERENCES......Page 1084
II. INSULIN’S ROLE IN PHYSIOLOGY......Page 1092
A. Insulin Structure......Page 1093
1. The Role of Zinc in Insulin Solubility......Page 1094
3. Early Efforts to Prolong Insulin Action......Page 1095
3. Insulin Polymer Matrix Preparation......Page 1096
2. Mechanism of Release......Page 1097
4. In Vivo Insulin Delivery......Page 1098
6. Effect of pH on Insulin Release......Page 1099
V. A GLUCOSE MEDIATED INSULIN DELIVERY IMPLANT......Page 1100
2. In Vitro Release of Insulin in Response to a Glucose Stimulus......Page 1101
C. In Vivo Study Methods......Page 1102
VI. DISCUSSION......Page 1103
VII. CONCLUSIONS......Page 1104
REFERENCES......Page 1105
A. Anatomy and Functions of the Kidney......Page 1107
C. Transport Systems: The Tubules......Page 1108
A. Renal Handling of Low-Molecular-Weight Proteins......Page 1109
C. Potentials and Limitations of Low-Molecular-Weight Proteins as Renal Drug Carriers......Page 1110
D. How Chemically to Link an ACE Inhibitor to a Low-Molecular-Weight Protein......Page 1111
1. Conjugation via the Carboxylic Acid Group......Page 1112
2. Conjugation via the Amino Group: Lisinopril......Page 1116
3. Conjugation via the Thiol Group: Captopril......Page 1117
5. Discussion and Conclusions......Page 1118
B. Nonsteroidal Anti-In.ammatory Drugs......Page 1119
1. Naproxen–lysozyme......Page 1120
2. Effects of Angiotensin II and ACE Inhibitors......Page 1121
3. Captopril–Lysozyme......Page 1122
D. Doxorubicin......Page 1123
1. Doxorubicin–Lysozyme......Page 1124
V. CONCLUDING REMARKS......Page 1125
REFERENCES......Page 1126